What happens when you take prednisone with licorice?
Real licorice root contains glycyrrhizin (also called glycyrrhizic acid), which is hydrolyzed in the gut to glycyrrhetinic acid. Glycyrrhetinic acid inhibits the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2), which normally converts active cortisol into inactive cortisone at the mineralocorticoid receptor in the kidney. When 11-beta-HSD2 is inhibited, both endogenous cortisol and exogenous glucocorticoids like prednisolone (the active form of prednisone) accumulate in mineralocorticoid-receptor-containing tissues and activate those receptors as if they were aldosterone.
The result is a state called pseudohyperaldosteronism: the body acts as though aldosterone levels are sky-high, even though they are actually low. Sodium and water are retained, blood pressure rises, and potassium and hydrogen ions are excreted in large amounts. Hypokalemia and metabolic alkalosis follow, and the loss of potassium can become severe enough to cause muscle paralysis, rhabdomyolysis, and cardiac arrhythmias.
On top of this, glycyrrhetinic acid also inhibits some of the enzymes that metabolize glucocorticoids in the liver, extending the half-life and raising peak concentrations of prednisolone in the bloodstream. So the combination of prednisone with licorice both prolongs the steroid effect and amplifies its mineralocorticoid component. The interaction is well documented in pharmacology textbooks and case reports.
Why is this important?
Prednisone alone causes some potassium loss through its weak intrinsic mineralocorticoid activity, but the magnitude is usually modest at typical anti-inflammatory doses. Add licorice glycyrrhizin and the picture changes dramatically. Healthy volunteer studies have shown plasma potassium falling by 0.3 to 1.5 mEq/L in subjects ingesting licorice 100 to 200 grams per day for one to four weeks, with several subjects requiring withdrawal from the study because of severe hypokalemia. Layer that onto a patient already on prednisone, and clinically dangerous hypokalemia can develop in days to weeks.
The literature contains case reports of patients on chronic glucocorticoid therapy developing severe hypokalemic paralysis, refractory hypertension, hypokalemic rhabdomyolysis, and cardiac arrhythmias after starting habitual licorice consumption. Older patients, patients with cardiovascular disease, patients on diuretics or laxatives, and patients with reduced renal function are at highest risk.
Many users do not realize that the licorice candy, herbal tea, or traditional Chinese medicine formulation they are consuming contains pharmacologically active glycyrrhizin. Some patients chew licorice gum or eat licorice candy daily for stress or digestive complaints. Others use licorice-containing herbal blends for cough, sore throat, or adrenal support. All of these can interact with prednisone.
What should you do?
If you are taking prednisone, avoid licorice root, licorice candy, licorice tea, and herbal supplements containing licorice or glycyrrhizin. This includes black licorice candy made from real licorice extract (most American red licorice candy is artificially flavored and not a problem; check the ingredient list), licorice root herbal teas, herbal cough drops with licorice, and traditional Chinese medicine formulations containing gan cao (which is licorice root).
If you currently consume licorice products and need to start prednisone, stop the licorice and inform your prescriber. If you have been taking both, discuss with your clinician whether to check your serum potassium and blood pressure, taper off the licorice, and watch for symptoms of hypokalemia (muscle weakness, cramping, constipation, palpitations, fatigue) over the following days.
Deglycyrrhizinated licorice (DGL) is a licorice extract with glycyrrhizin removed. It is sold as chewable tablets for heartburn and digestive complaints and does not produce the mineralocorticoid effects. DGL is therefore acceptable to use while on prednisone, though as with any supplement during steroid therapy, it is worth mentioning to your clinician.
If you develop muscle weakness, leg cramps, palpitations, swelling, or unexplained fatigue while on prednisone, particularly if you have been consuming licorice, get your potassium level checked promptly. Severe hypokalemia is a medical emergency.
Which specific products are affected?
Real licorice products contain glycyrrhizin. These include black licorice candy made with licorice extract (Twizzlers Black, Panda licorice, Australian-style soft licorice, Dutch drop), licorice root herbal teas (Yogi Egyptian Licorice, Traditional Medicinals Organic Licorice Root), licorice root powder and capsules sold in health food stores, and many herbal blends marketed for adrenal support, sore throat, or digestive health.
Traditional Chinese medicine uses licorice root (gan cao) as a harmonizer in many formulations. Patients using TCM herbal blends should ask their prescriber to identify any glycyrrhizin-containing components.
Some chewing gums and lozenges contain licorice flavoring; check labels if you are unsure. Anise-flavored products are sometimes confused with licorice but do not contain glycyrrhizin and are unrelated to this interaction.
Deglycyrrhizinated licorice (DGL) products, such as Enzymatic Therapy DGL, NOW Foods DGL, and similar chewable tablets, have the active compound removed and are safe to use during prednisone therapy.
The interaction applies across the glucocorticoid class. Prednisone, prednisolone, methylprednisolone, hydrocortisone (especially at supraphysiologic doses), and dexamethasone all combine with licorice in ways that can amplify mineralocorticoid effects and worsen hypokalemia, though hydrocortisone is particularly potent in this combination because of its higher native mineralocorticoid activity.
Other drugs that lower potassium can compound the risk further. Loop diuretics (furosemide), thiazide diuretics (hydrochlorothiazide), and amphotericin B all add to the potassium-wasting effect when combined with prednisone plus licorice.
The bottom line
Licorice glycyrrhizin inhibits the enzyme that normally limits mineralocorticoid receptor activation by glucocorticoids, turning the modest sodium-retaining and potassium-wasting effect of prednisone into a much larger and clinically dangerous one. Avoid real licorice products (candy, tea, herbal supplements, TCM formulations) while on prednisone. Deglycyrrhizinated licorice (DGL) is fine. Watch for muscle weakness, palpitations, swelling, and rising blood pressure, and have your potassium checked if you have been consuming both.